International Journal of Epidemiology 2002;31:413-419
© International Epidemiological Association 2002
Life Course Epidemiology |
Fetal environment and subsequent obesity: a study of maternal smoking
Institute of Child Health, Centre for Paediatric Epidemiology and Biostatistics, 30 Guilford Street, London WC1N 1EH, UK. E-mail: c.power{at}ich.ucl.ac.uk
Abstract
Background The intrauterine environment may influence the development of obesity, but as yet, the long-term effect of growth in utero is unclear. We studied maternal smoking during pregnancy to gain insight on how an insult affecting fetal growth might subsequently influence obesity risk through childhood to age 33.
Methods Data from the 1958 British birth cohort (all births in England, Wales and Scotland, 3–9 March 1958), including body mass index (BMI), maternal smoking during pregnancy and several potential confounding factors. We assessed obesity risk at ages 7, 11, 16, 23 and 33 associated with maternal smoking. Adjusted odds ratios (OR) for obesity at age 33 were estimated for 2918 men and 2921 women with complete data.
Results Infants of mothers who smoked in pregnancy were lighter at birth than infants of non-smokers, but from adolescence (age 11 for females, 16 for males) they had an increased risk of being in the fattest decile of BMI. The OR for obesity associated with maternal smoking increased with age, suggesting strengthening of the relationship over time. At age 33 the OR was 1.56 (95% CI : 1.22–2.00) for men and 1.41 (95% CI : 1.12–1.79) for women. This was robust to adjustment for factors in early life, childhood and adulthood.
Conclusions An elevated risk of obesity among the offspring of smokers was not accounted for by other known influences. Findings are consistent with a long-term effect of intrauterine environment on adiposity, possibly through fetal nutrition, although other mechanisms should be investigated in future studies of obesity.
Keywords Obesity, body mass index, smoking, pregnancy, fetal origins, critical period, child, adult, growth, cohort studies
Accepted 16 November 2001
Obesity has been identified as an escalating problem worldwide, and is associated with a significant disease burden.1,2 The causes underlying the development of obesity are therefore of considerable public health importance. Adult lifestyles are emphasized in much research, but it is increasingly suspected that the intrauterine period is critical in the development of obesity.3 Greater maternal size and weight gain tend, in general, to be related to greater body mass index (BMI) among offspring.4 Yet, counter to this is the evidence from the Dutch Hunger Winter Study, implicating maternal undernutrition in the first and second trimesters of pregnancy in the development of obesity.5,6 Given this conflicting evidence, it is unclear whether poor fetal growth subsequently promotes the development of obesity.
Some studies have examined associations between birthweight and obesity, but in general, they have neglected potential confounding effects, which may be particularly strong for parental body size.4 A recent study, based on the 1958 birth cohort, showed that a weak positive association between birthweight and adult BMI was abolished after adjustment for maternal weight.7 However, studies relying on birthweight as a proxy for fetal growth may obscure a distinct effect of poor intrauterine environment on obesity. This is because there are strong associations between parental size, offspring birthweight and subsequent size through to adulthood. Other models that elucidate the role of fetal environment in the development of obesity are therefore needed.
Maternal smoking during pregnancy is a potentially useful measure which, after 40 years of research,8 is recognized as having deleterious effects on fetal growth9 and potentially, provides a natural experiment to assess long-term effects on obesity. Previous studies show catch-up growth among those exposed to tobacco in utero,10–12 but with the longest follow-up being to adolescence13 evidence is lacking on obesity risk through to adulthood. Thus, our aim is to determine whether maternal smoking during pregnancy influences the risk of obesity among offspring at different life stages from childhood through to early adulthood and whether any maternal smoking effect is accounted for by known risk factors, including parental size, own diet and smoking habit. The nationally representative British cohort of births in 1958 followed through to age 33 is used for this study.
Methods
Sample
The 1958 birth cohort includes all individuals born in England, Wales and Scotland, 3–9 March 1958. Details of the study are presented elsewhere.14 In brief, information was obtained on 98% of births totalling 17 414, with follow-up of survivors at ages 7, 11, 16, 23 and 33 years (11 405 subjects were included in the 33-year survey).15 Multiple births (n = 446) are excluded from all analyses. Biases associated with sample attrition have tended to be small, although in the direction of under representing more deprived social groups over time.14 In the sample used here for multivariate analysis, 19.5% of men were born into social classes IV & V or had no male head of household, compared with 23.9% in the original birth survey; for women proportions are 21.0% and 24.6%, respectively. Mean birthweight was significantly heavier in the sample used for multivariate analysis than in the original survey: 3.45 kg and 3.38 kg, respectively, for males; 3.29 kg and 3.25 kg for females. Mean BMI at 33 years was identical in samples with and without complete data on all confounding factors (25.6 kg/m2 for men and 24.6 kg/m2 for women).
Measures
Height and weight were: (1) measured by trained medical personnel at 7, 11 and 16 years (subjects were weighed in underclothes to the nearest pound, and height was measured to the nearest inch); (2) self-reported at age 23; (3) measured at age 33 (height, without shoes using a stadiometer reading to the nearest centimetre; weight, in indoor clothing using Salter portable scales). Data were checked to detect coding errors.16 Body mass index was calculated as kg/m2 by sex for each age, using the 90th percentile of the sample to define the fattest group, with values as follows:
In more detailed analysis of adult obesity we used a BMI cutoff of 
30 kg/m.2,17 Women who were pregnant at age 33 (n = 256) were excluded from analyses. Birthweight (recorded as pounds and ounces and converted into kilograms) and gestational age were obtained at birth from a questionnaire completed by the midwife at delivery or shortly afterwards. Gestational age was determined from the date of the first day of the last menstrual period.
Maternal smoking was recorded in the questionnaire at birth as number of cigarettes smoked per day after the fourth month of pregnancy. This classification of the smoking data was adopted in the original birth survey report, because at the time (1969), it was expected that maternal smoking exerted a maximum effect on birthweight in the later period of pregnancy.18 As many women changed their smoking habits in the early months of pregnancy, it was difficult to group smoking from the beginning of pregnancy. Mothers were categorized as non-smokers (<1 cigarette per day), or smokers (1 cigarette per day). In further analysis, they were grouped according to daily cigarette consumption into light (1–9), medium (10–19) or heavy smokers (>20). Mothers also reported smoking prior to pregnancy: 99% (n = 5568) of smokers during pregnancy had smoked prior to pregnancy; 89% (n = 9923) of non-smokers during pregnancy did not smoke prior to pregnancy.
Potential confounding factors
Several potential confounding factors were identified a priori, including: parental body size, maternal age, infant feeding, parity, social class, own education level, smoking and diet. Data are as follows: parental height (to nearest inch) and weight (in half stones), recorded in 1969 and converted, respectively, to metres and kilograms. A BMI was derived for each parent. Parity was coded as 0, 1 or >1. Infant feeding was coded as whether the infant was breastfed or not. Social class based on the Registrar General's classification was grouped into four categories: I & II (professional and managerial), III non-manual (unskilled); III manual (skilled) and IV & V (semi and unskilled manual). Class at birth and age 7 was based on father's occupation (single mother households were classified with IV & V), and at 23 and 33 years, on the man or woman's own occupation. Educational qualifications of the cohort were classified as above ‘A’ Level, ‘A’ Level or equivalent, ‘O’ Level or equivalent, less than ‘O’ Level, and no qualifications. Smoking behaviour was categorized as: (1) persistent regular smoker (>1 cigarette per day) at both 23 and 33 years, (2) other smokers, and (3) non-smokers. Physical inactivity was ascertained at age 23 as how often the cohort member watched television in the last 4 weeks. This was coded as >5, 3–4 and 1–2 times per week or 0–3 times in the last 4 weeks. Diet was assessed from a food frequency questionnaire at age 33, with consumption coded as more or less than once weekly for (1) fatty foods (fried food and chips), (2) fresh fruit (in summer) or raw vegetables and salads (in winter), and (3) biscuits, sweets and chocolate.
Data analysis
The relationship between maternal smoking during pregnancy and BMI of the cohort member was estimated separately for each age and sex, using odds ratios (OR) for obesity in those exposed to tobacco prenatally versus those not exposed. The trend in the OR for obesity over the five ages was tested using a repeated measures multilevel model, with both linear and quadratic terms.19 Further comparisons were made for mean BMI, with transformed (natural log) BMI to approximate normality from a positively skewed distribution. Standard deviation scores (z-scores) were calculated for each age and sex group to allow for differences in variance for childhood BMI. In more detailed analysis of obesity at 33 years, we assessed whether potential confounding factors, such as parental BMI, could account for the association with maternal smoking. Initially, we investigated bivariate relationships with potential confounding factors. Several factors were significantly associated with maternal smoking (Table 1
). Compared with non-smokers, mothers who smoked after the fourth month of pregnancy had a lower BMI (in 1969), higher parity, babies of lower birthweight and gestational age, lower social class in 1958 and 1964; and offspring who, on average, had lower qualifications, lower social class and poorer health behaviours in their early adulthood. However, many potential confounding factors were unrelated to obesity at age 33 (P > 0.05 in t-test or 
2 test) and were therefore excluded from further analyses. The effect of maternal smoking on obesity at age 33 was estimated in logistic regression models with and without adjustment for potential confounding factors. These multivariate analyses were conducted on a reduced sample with complete data (2918 males; 2921 females). A sensitivity analysis was undertaken, including all subjects with data on maternal smoking in pregnancy and 33-year BMI (5047 men; 4995 women) with an additional ‘missing’ category identified for each potential confounding factor separately. Results obtained from this analysis were similar to those reported here for the restricted sample with complete data.
|
The analyses were conducted according to the chronological order of the covariates, ordered in four stages: (1) maternal BMI, (2) maternal BMI and other early life (birth) factors, (3) early life and childhood factors (age 7), and (4) early life, childhood and adult life factors. Although birthweight was included as a co-variate in these models, it was regarded not as a confounding factor, but as an intermediate factor, i.e. representing a potential pathway through which effects of maternal smoking might operate. No significant interactions were found between maternal smoking and other main effect variables. Linear regression analyses using BMI (natural log-transformed) at 33 years, with the same predictor variables were carried out in parallel.
Throughout the analyses we used a dichotomous categorization of maternal smoking in order to retain a group of women smokers reporting variable consumption of cigarettes (n = 967). However, we conducted additional analyses excluding these women, to investigate whether amount smoked during pregnancy had a dose-response relationship with offspring BMI. To further clarify whether an association with BMI was due to maternal smoking rather than to inadequate measures of confounding factors, we compared mothers who continued to smoke during pregnancy with those who quit.
Results
Of 16 766 singletons with information on maternal smoking, 5624 mothers (33.5%) smoked after the fourth month of their pregnancy in 1958. Table 1
shows that, as demonstrated previously for this cohort,20 infants of women who smoked in pregnancy were lighter at birth than infants of non-smokers (3.28 kg versus 3.44 kg for males; 3.14 kg versus 3.30 kg for females). Yet, children of smokers had an elevated risk of being in the fattest decile of BMI, which was significant by 11 and 16 years, respectively, for females and males (Table 2). The OR associated with maternal smoking showed a significant quadratic trend over the five ages 7 to 33 (P < 0.05), representing an increase to age 23, which did not continue through to 33 years. However, the increase from childhood (ages 7, 11 and 16) to adulthood (age 33) was significant (linear trend P < 0.05), suggesting a strengthening of the relationship between maternal smoking and obesity. The greater BMI of children whose mothers smoked in pregnancy is also evident from a comparison of means (Table 2) and associated z-scores.
|
Using a standard definition of adult obesity (BMI
30) at age 33, the unadjusted OR associated with maternal smoking was 1.40 (95% CI : 1.17–1.68) for men and 1.43 (95% CI : 1.20– 1.70) for women in the full sample. For the 2918 males and 2921 females with complete data available for multivariate analysis, the unadjusted OR was respectively, 1.56 and 1.41 (Table 3). After adjustment for maternal BMI the OR increased due to negative confounding. Further adjustment for early life factors (birthweight, infant feeding and social class at birth) slightly reduced the OR. With additional adjustment for childhood social class and adult factors (including several measures of diet, physical inactivity, education and social class) the OR for obesity remained significantly elevated for men (1.55, 95% CI : 1.19–2.00) and for women (1.44, 95% CI : 1.13–1.84) (Table 3). The risk associated with maternal smoking was therefore largely unaffected by adjustment for several confounding factors. Linear regression analysis of ln BMI at 33 years also showed a significant effect of maternal smoking, which was robust to adjustment for confounding factors (data not presented).
|
Testing for a dose response in prevalence of obesity according to maternal smoking habit revealed significant linear trends at ages 16 and 33 years. At 33 years, 10.3% of offspring of non-smokers were obese compared to 13.4% of light smokers, 15.0% of medium smokers and 16.0% of heavy smokers (linear trend P = 0.012). Finally, we compared offspring whose mothers continued to smoke during pregnancy (n = 5568) with those whose mothers quit smoking during pregnancy (n = 1219). Offspring of persistent smokers had a higher prevalence of obesity than offspring of ‘quitters’, consistently at ages 16, 23 and 33 years. For example at 33 years, 14.2% of the offspring of continuing smokers were obese, compared to 10.2% of offspring whose mothers quit smoking during pregnancy (P < 0.005).
Discussion
In this British cohort, offspring born to mothers who smoked during pregnancy in 1958 were lighter at birth, but had a greater risk of obesity over the subsequent three decades through to mid-adulthood. The risk associated with maternal smoking appeared to strengthen with increasing age of offspring, it was not accounted for by several potential confounding factors, and paradoxically, was not reduced after adjustment for birthweight. By age 33 the offspring of smokers had about a 40% elevated risk of obesity compared with offspring of non-smokers. Thus, prenatal exposure to tobacco in this study sample appears to be associated with subsequent gain in weight among both males and females. Weight gain related to maternal smoking in pregnancy has been reported previously10,21–23 but in studies largely confined to the first decade of life and thus they were unable to demonstrate effects on obesity in adulthood. Longer-term follow-up is important because gains in weight over a short period may be interpreted as reassuring,22 and may obscure the extent of growth disturbance. Prenatal tobacco exposure has rarely been used explicitly to test whether poor fetal growth adversely affects an individual's risk of subsequent overweight,11,13 despite the suggestion that it provides an appropriate test.24 Some consistencies are emerging across studies, but there are also apparent contradictions and methodological considerations to be addressed.
Methodological considerations
Specifically in this cohort, data on maternal smoking was categorized in the original birth survey as occurring before or after the fourth month of pregnancy. As mentioned previously, this categorization was used because of contemporary expectations about when maternal smoking exerted its maximum effect,18 an expectation which is supported by more recent research.9 Comparing maternal smoking status on two occasions, i.e. prior to and during pregnancy, we found that most mothers (99%) smoking in pregnancy also reported smoking before: they are therefore likely to have smoked throughout their pregnancy. (Reporting biases in smoking behaviour in 1958 are unlikely given that knowledge of adverse effects on offspring was limited at that time.) Consequently, as in previous studies of maternal smoking and adiposity of offspring, the risk of obesity associated with prenatal tobacco exposure was not differentiated according to stage of pregnancy. Regarding losses to follow-up, few sample biases have been identified for this cohort sample and the results are therefore likely to apply to contemporary young adults.
Importantly, this study was able to take account of other known influences on obesity, which could potentially confound the relationship with maternal smoking. The information available for different ages represents potential lifetime confounding exposures and this is a major strength of our study. Parental BMI is perhaps the most salient potential confounder, due to its powerful influence on adiposity among offspring,25 yet this factor failed to account for the maternal smoking-offspring BMI relationship. Other potentially important factors include diet, physical inactivity and offspring's own smoking habits. Neither infant feeding nor adult diet at age 33 (frequency of consumption of fatty or sugary foods and fruit or vegetable consumption) affected the obesity risk associated with maternal smoking in pregnancy. This is unsurprising given the modest differences in adult diet between offspring of smokers and non-smokers detected with the measures available in this study. We cannot discount the possibility that more precise measurement of adult diet or dietary intake in childhood might account for our findings, although social class at birth and at age 7 provide additional proxy measures for dietary intake. There is evidence from earlier studies26,27 and contemporary research28 that diet is socially patterned, with children from manual class backgrounds having poorer diets as indicated by more frequent consumption of sweets, sweet drinks and less frequent consumption of healthy foods. Sedentary behaviour was indicated by television viewing, which has previously been shown to relate to changes in BMI over time.29,30 Confounding effects of own smoking behaviour were also negligible, largely because persistent smoking was not related to adult obesity. To further discount the possibility that the maternal smoking-obesity association was due to residual confounding, we compared the offspring of persistent smokers and of quitters. That the offspring of persistent smokers had a greater prevalence of obesity at 16, 23 and 33 years, lends weight to the conclusion that there is a relationship between maternal smoking and later obesity. Moreover, the significant dose-response relationship between maternal smoking and obesity prevalence provides additional support for the association.
Comparison with other studies
It is difficult to compare our findings with more direct evidence linking maternal nutrition to overweight among their offspring. Indirect evidence comes from studies of birthweight, but paradoxically, these generally show a positive relationship with BMI increasing with increasing weight at birth.4 The birthweight-BMI association tends to be weak, and within this cohort appears to be due to underlying relationships with parental body size.7 More direct evidence on maternal nutrition is available from the Dutch Hunger Winter Study. Exposure to famine in the first half of pregnancy increased the risk of obesity among surviving offspring, whilst famine in the last trimester and postnatally was associated with a reduced risk, suggesting that effects depend on the timing of intrauterine exposure.5,6 It should be noted, however, that even within the Dutch study, relationships have varied by gender and with increasing age of those exposed to famine prenatally. Initially, a study of male conscripts showed a famine effect on rates of obesity at age 19; whereas, a more recent study showed adverse effects on body weight, BMI and waist circumference at age 50 in women, but not men.6 No association was found between famine exposure in Leningrad and BMI at age 52–53 years.31
Research on maternal smoking and subsequent growth shows more consistent effects. Most studies suggest a greater weight gain across differing periods of childhood among offspring of mothers who smoked during pregnancy.10,11,13,21–23,32 But there are exceptions, including one study showing a lower weight gain to 6.5 years in offspring of smokers,33 although elsewhere, a weight and height deficit in 3-year-old children of smokers was not significant after allowing for maternal social and obstetric factors.34 Yet, on the basis of the changing relationship of maternal smoking to obesity with age in the 1958 cohort, we might expect the effect of maternal smoking to vary for different populations surveyed at different ages.
Strengthening effect with increasing age or temporal changes?
We do not interpret the apparent strengthening relationship as an amplification of a latent effect with increasing age, rather it is more likely to reflect temporal changes in postnatal exposures. The 1958 cohort grew up during a period of nutritional abundance and increasingly high fat diets.35 The most parsimonious explanation for the strengthening relationship is that the effect of prenatal exposure to tobacco, possibly acting through restricted fetal growth, increases with the energy density of the postnatal diet. This explanation would also account for the different effects observed in the Dutch and Leningrad famine studies. Individuals exposed in utero to the Dutch famine grew up in a time of increasing affluence, whilst, in the Leningrad famine31 individuals endured a longer period of food shortage and a less abundant diet subsequently.6 Thus, the effect of early life environment may depend on subsequent exposures at other life stages.
However, we would emphasize that the mechanisms involved are unclear at this stage and that the explanation presented here may even appear to be counter-intuitive, given that we found no evidence that fetal growth, as represented by birthweight, acted as an intermediate factor on adult obesity. (This was also shown in the Dutch Hunger Winter Study, in which the association between exposure to famine in early gestation and obesity at 50 years in women was reported to be independent of body size at birth.6) Yet, as we have shown elsewhere, the positive birthweight-BMI association is strongly influenced by maternal body size.7 Accordingly, in the present study, the effect of adjustment for birthweight mimicked that for maternal BMI, which had a negative confounding effect on the maternal smoking-offspring obesity relationship. Whilst it is not surprising, therefore, that the risk of adult obesity associated with maternal smoking did not reduce after allowing for weight at birth, we cannot conclude that a maternal smoking effect is independent of fetal growth.
Even though the relationship between maternal smoking and offspring growth retardation is a well-replicated finding, the underlying mechanism is not known. Potentially, nicotine may suppress the mother's appetite, inducing fetal growth retardation due to poor nutrition. Also, increased carbon monoxide levels in the maternal blood supply may reduce oxygen unloading to the fetus, affecting fetal growth and development. Alternatively, nicotine may produce vasoconstrictive effects on maternal and uteroplacental vasculature, or cyanide compounds may have toxic effects that interfere with fetal oxidative metabolism.36
Whatever the mechanisms, the potential for maternal smoking in pregnancy to affect growth patterns over the long-term is evident from studies of linear growth, with height deficits documented in childhood37,38 through to adulthood.39 Disproportionate weight gain associated with prenatal tobacco exposure may be due to the infant's self-regulation of food intake after birth, as suggested by Ounsted's40 study showing that small-for-date babies take more bottle milk per kilogram bodyweight than large-for-date babies. Alternatively, endocrine imbalances could occur through disrupted programming of endocrine axes at critical developmental periods, as proposed by the fetal origins hypothesis. Our study does not shed any light on whether maternal nutrition or fetal growth underlie the processes through which subsequent body size and shape are affected, but it represents an important first stage, establishing a long-term association with adiposity. Thus, our results are consistent with the fetal origins hypothesis that gestation is a critical period in the development of obesity. They also provide some support for the thrifty phenotype hypothesis, whereby conditions in utero influence subsequent development of insulin resistance and glucose intolerance in adulthood.41 Specifically in relation to smoking, our study is further evidence that long-term health consequences are not confined to one generation, but that the health of a future generation is also impaired.
KEY MESSAGES
|
|
Acknowledgments
The research was supported by the Canadian Institute for Advanced Research. We thank Leah Li for statistical advice.
References
1 World Health Organization. Obesity: Preventing and Managing the Global Epidemic. Report of a WHO Consultation on Obesity. Geneva: WHO, 1998.
2
Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity. JAMA 1999;282:1523–29.
3 Whitaker RC, Dietz WH. Role of the prenatal environment in the development of obesity. J Pediatr 1998;132:768–76.[CrossRef][Web of Science][Medline]
4 Parsons TJ, Power C, Logan S, Summerbell CD. Childhood predictors of adult obesity: a systematic review. Int J Obes Relat Metab Disord 1999;23(Suppl.8):S1–107.
5 Ravelli GP, Stein ZA, Susser MW. Obesity in young men after famine exposure in utero and early infancy. N Engl J Med 1976;295:349–53.[Abstract]
6
Ravelli AC, Der Meulen JH, Osmond C, Barker DJ, Bleker OP. Obesity at the age of 50 years in men and women exposed to famine prenatally. Am J Clin Nutr 1999;70:811–16.
7
Parsons T, Power C, Manor O. Fetal and early life growth and body mass index from birth to early adulthood in the 1958 British birth cohort: a longitudinal study. BMJ 2001;323:1331–35.
8 Simpson WJ, Linda L. A preliminary report on cigarette smoking and the incidence of prematurity. Am J Obstet Gynecol 1957;73:808–15.[Web of Science]
9 Kramer MS. Determinants of low birth weight: methodological assessment and meta-analysis. Bull World Health Organ 1987;65:663–737.[Web of Science][Medline]
10 Vik T, Jacobsen G, Vatten L, Bakketeig LS. Pre- and post-natal growth in children of women who smoked in pregnancy. Early Hum Dev 1996;45:245–55.[CrossRef][Web of Science][Medline]
11
Ong KK, Ahmed ML, Emmett PM, Preece MA, Dunger DB. Association between postnatal catch-up growth and obesity in childhood: prospective cohort study. BMJ 2000;320:967–71.
12 Sowan NA, Stember ML. Parental risk factors for infant obesity. MCN Am J Matern Child Nurs 2000;25:234–40.[CrossRef][Medline]
13
Williams S, Poulton R. Twins and maternal smoking: ordeals for the fetal origins hypothesis? A cohort study. BMJ 1999;318:897–900.
14 Ferri E (ed.). Life at 33. The Fifth Follow-up of the National Child Development Study. London: National Children's Bureau, 1993.
15 Centre for Longitudinal Studies IoE. National Child Development Study Composite File Including Selected Perinatal Data and Sweeps One to Five [computer file]. National Birthday Trust Fund, National Children's Bureau, City University Social Statistics Research Unit [original data producers]. The Data Archive distributor. Colchester, Essex. SN: 3148. 1994.
16 Power C, Moynihan C. Social class and changes in weight-forheight between childhood and early adulthood. Int J Obes 1988; 12:445–53.[Web of Science][Medline]
17 Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: executive summary. Expert Panel on the Identification, Evaluation, and Treatment of Overweight in Adults. Am J Clin Nutr 1998;68:899–917.[Web of Science][Medline]
18 Butler NR, Alberman E (eds). Perinatal Problems. The Second Report of the British Perinatal Mortality Survey. London & Edinburgh: E & S Livingstone Ltd, 1969.
19 Goldstein H. Multilevel Statistical Models. 2nd Edn. London: Institute of Education, 1995.
20 Butler NR, Goldstein H, Ross EM. Cigarette smoking in pregnancy: its influence on birth weight and perinatal mortality. BMJ 1972;ii: 127–30.
21
Nafstad P, Jaakkola JJ, Hagen JA et al. Weight gain during the first year of life in relation to maternal smoking and breast feeding in Norway. J Epidemiol Community Health 1997;51:261–65.
22
Conter V, Cortinovis I, Rogari P, Riva L. Weight growth in infants born to mothers who smoked during pregnancy. BMJ 1995;310:768–71.
23 Blake KV, Gurrin LC, Evans SF et al. Maternal cigarette smoking during pregnancy, low birth weight and subsequent blood pressure in early childhood. Early Hum Dev 2000;57:137–47.[CrossRef][Web of Science][Medline]
24
Paneth N, Susser M. Early origin of coronary heart disease (the ‘Barker hypothesis’). BMJ 1995;310:411–12.
25
Whitaker RC, Wright JA, Pepe MS, Seidel KD, Dietz WH. Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med 1997;337:869–73.
26 Golding J, Haslum M, Morris AC. What do our ten-year old children eat? Health Visitor 1984;57:178–79.[Medline]
27 Department of Health. The Diets of British Schoolchildren. RHSS 36. London: HMSO, 1989.
28 Gregory J, Lowe S. National Diet and Nutrition Survey. Young People aged 4–18 Years. Vol. 1. Report of the Diet and Nutrition Survey. London: Stationery Office, 2000.
29 Berkey CS, Rockett HR, Field AE et al. Activity, dietary intake, and weight changes in a longitudinal study of preadolescent and adolescent boys and girls. Pediatrics 2000;105:E56.
30
Dietz WH Jr, Gortmaker SL. Do we fatten our children at the television set? Obesity and television viewing in children and adolescents. Pediatrics 1985;75:807–12.
31
Stanner SA, Bulmer K, Andres C et al. Does malnutrition in utero determine diabetes and coronary heart disease in adulthood? Results from the Leningrad siege study, a cross sectional study [see comments]. BMJ 1997;315:1342–48.
32 Jacobson JL, Jacobson SW, Sokol RJ. Effects of prenatal exposure to alcohol, smoking, and illicit drugs on postpartum somatic growth. Alcohol Clin Exp Res 1994;18:317–23.[CrossRef][Web of Science][Medline]
33 Dunn HG, McBurney AK, Ingram S, Hunter CM. Maternal cigarette smoking during pregnancy and the child's subsequent development: I. Physical growth to the age of 61 /2 years. Can J Public Health 1976;67:499–505.[Web of Science][Medline]
34
Fox NL, Sexton M, Hebel JR. Prenatal exposure to tobacco: I. Effects on physical growth at age three. Int J Epidemiol 1990;19:66–71.
35
Prentice AM, Jebb SA. Obesity in Britain: gluttony or sloth? BMJ 1995;311:437–39.
36 Horta BL, Victora CG, Menezes AM, Halpern R, Barros FC. Low birthweight, preterm births and intrauterine growth retardation in relation to maternal smoking. Paediatr Perinat Epidemiol 1997;11:140–51.[CrossRef][Web of Science][Medline]
37 Butler NR, Goldstein H. Smoking in pregnancy and subsequent child development. BMJ 1973;(892):573–75.
38 Rantakallio P. A follow-up study up to the age of 14 of children whose mothers smoked during pregnancy. Acta Paediatr Scand 1983;72:747–53.[Web of Science][Medline]
39 Fogelman KR, Manor O. Smoking in pregnancy and development in to early adulthood. BMJ 1988;297:1233–36.
40 Ounsted M, Sleigh G. The infant's self-regulation of food intake and weight gain. Difference in metabolic balance after growth constraint or acceleration in utero. Lancet 1975;i:1393–97.
41 Hales CN, Barker DJ. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 1992;35:595–601.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. M. Rogge The Role of Impaired Mitochondrial Lipid Oxidation in Obesity Biol Res Nurs, April 1, 2009; 10(4): 356 - 373. [Abstract] [PDF]
|
|
|
|
 |
|
 C. C. Geerts, M. L. Bots, D. E. Grobbee, and C. S.P.M. Uiterwaal Parental Smoking and Vascular Damage in Young Adult Offspring: Is Early Life Exposure Critical?: The Atherosclerosis Risk in Young Adults Study Arterioscler Thromb Vasc Biol, December 1, 2008; 28(12): 2296 - 2302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Somm, V. M. Schwitzgebel, D. M. Vauthay, E. J. Camm, C. Y. Chen, J.-P. Giacobino, S. V. Sizonenko, M. L. Aubert, and P. S. Huppi Prenatal Nicotine Exposure Alters Early Pancreatic Islet and Adipose Tissue Development with Consequences on the Control of Body Weight and Glucose Metabolism Later in Life Endocrinology, December 1, 2008; 149(12): 6289 - 6299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Sharma, M. E. Cogswell, and R. Li Dose-Response Associations Between Maternal Smoking During Pregnancy and Subsequent Childhood Obesity: Effect Modification by Maternal Race/Ethnicity in a Low-Income US Cohort Am. J. Epidemiol., November 1, 2008; 168(9): 995 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Bruin, H. C. Gerstein, K. M. Morrison, and A. C. Holloway Increased Pancreatic Beta-Cell Apoptosis following Fetal and Neonatal Exposure to Nicotine Is Mediated via the Mitochondria Toxicol. Sci., June 1, 2008; 103(2): 362 - 370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Syme, M. Abrahamowicz, G. T. Leonard, M. Perron, A. Pitiot, X. Qiu, L. Richer, J. Totman, S. Veillette, Y. Xiao, et al. Intra-abdominal Adiposity and Individual Components of the Metabolic Syndrome in Adolescence: Sex Differences and Underlying Mechanisms Arch Pediatr Adolesc Med, May 1, 2008; 162(5): 453 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kivimaki, D. A Lawlor, G. D. Smith, M. Elovainio, M. Jokela, L. Keltikangas-Jarvinen, J. S. Viikari, and O. T Raitakari Substantial intergenerational increases in body mass index are not explained by the fetal overnutrition hypothesis: the Cardiovascular Risk in Young Finns Study Am. J. Clinical Nutrition, November 1, 2007; 86(5): 1509 - 1514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Shulruf, S. Morton, F. Goodyear-Smith, C. O'Loughlin, and R. Dixon Designing Multidisciplinary Longitudinal Studies of Human Development: Analyzing Past Research to Inform Methodology Eval Health Prof, September 1, 2007; 30(3): 207 - 228. [Abstract] [PDF]
|
|
|
|
 |
|
 C. C. Geerts, D. E. Grobbee, C. K. van der Ent, B. M. de Jong, M. M. van der Zalm, N. van Putte-Katier, J. L.L. Kimpen, and C. S.P.M. Uiterwaal Tobacco Smoke Exposure of Pregnant Mothers and Blood Pressure in Their Newborns: Results from the Wheezing Illnesses Study Leidsche Rijn Birth Cohort Hypertension, September 1, 2007; 50(3): 572 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Ansari RE: "DOES MATERNAL SMOKING DURING PREGNANCY HAVE A DIRECT EFFECT ON FUTURE OFFSPRING OBESITY? EVIDENCE FROM A PROSPECTIVE BIRTH COHORT STUDY" Am. J. Epidemiol., August 15, 2007; 166(4): 490 - 490. [Full Text] [PDF]
|
|
|
|
|
|
D. A. Lawlor, D. A. Leon, and F. Rasmussen Growth Trajectory Matters: Interpreting the Associations among Birth Weight, Concurrent Body Size, and Systolic Blood Pressure in a Cohort Study of 378,707 Swedish Men Am. J. Epidemiol., June 15, 2007; 165(12): 1405 - 1412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Huxley, C. G Owen, P. H Whincup, D. G Cook, J. Rich-Edwards, G. D. Smith, and R. Collins Is birth weight a risk factor for ischemic heart disease in later life? Am. J. Clinical Nutrition, May 1, 2007; 85(5): 1244 - 1250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Stocker, E. Wargent, J. O'Dowd, C. Cornick, J. R. Speakman, J. R. S. Arch, and M. A. Cawthorne Prevention of diet-induced obesity and impaired glucose tolerance in rats following administration of leptin to their mothers Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2007; 292(5): R1810 - R1818. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Thomas, E. Hypponen, and C. Power Prenatal Exposures and Glucose Metabolism in Adulthood: Are effects mediated through birth weight and adiposity? Diabetes Care, April 1, 2007; 30(4): 918 - 924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. S Rogers, A. R Ness, C. D Steer, J. C. Wells, P. M Emmett, J. R Reilly, J. Tobias, and G. D. Smith Associations of size at birth and dual-energy X-ray absorptiometry measures of lean and fat mass at 9 to 10 y of age. Am. J. Clinical Nutrition, October 1, 2006; 84(4): 739 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Grun, H. Watanabe, Z. Zamanian, L. Maeda, K. Arima, R. Cubacha, D. M. Gardiner, J. Kanno, T. Iguchi, and B. Blumberg Endocrine-Disrupting Organotin Compounds Are Potent Inducers of Adipogenesis in Vertebrates Mol. Endocrinol., September 1, 2006; 20(9): 2141 - 2155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M Bartoshuk, V. B Duffy, J. E Hayes, H. R Moskowitz, and D. J Snyder Psychophysics of sweet and fat perception in obesity: problems, solutions and new perspectives Phil Trans R Soc B, July 29, 2006; 361(1471): 1137 - 1148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Power and J. Elliott Cohort profile: 1958 British birth cohort (National Child Development Study) Int. J. Epidemiol., February 1, 2006; 35(1): 34 - 41. [Full Text] [PDF]
|
|
|
|
|
|
A. Chen, M. L Pennell, M. A Klebanoff, W. J Rogan, and M. P Longnecker Maternal smoking during pregnancy in relation to child overweight: follow-up to age 8 years Int. J. Epidemiol., February 1, 2006; 35(1): 121 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Salsberry and P. B. Reagan Dynamics of Early Childhood Overweight Pediatrics, December 1, 2005; 116(6): 1329 - 1338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K Adams, H. E Harvey, and R. J Prince Association of maternal smoking with overweight at age 3 y in American Indian children Am. J. Clinical Nutrition, August 1, 2005; 82(2): 393 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. White, H. D. Braymer, D. A. York, and G. A. Bray Effect of a high or low ambient perinatal temperature on adult obesity in Osborne-Mendel and S5B/Pl rats Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2005; 288(5): R1376 - R1384. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. C. Mcmillen and J. S. Robinson Developmental Origins of the Metabolic Syndrome: Prediction, Plasticity, and Programming Physiol Rev, April 1, 2005; 85(2): 571 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Power, H. Graham, P. Due, J. Hallqvist, I. Joung, D. Kuh, and J. Lynch The contribution of childhood and adult socioeconomic position to adult obesity and smoking behaviour: an international comparison Int. J. Epidemiol., April 1, 2005; 34(2): 335 - 344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yang, C. A. Knight, M. M. Mamerow, K. Vickers, A. Penn, E. M. Postlethwait, and S. W. Ballinger Prenatal Environmental Tobacco Smoke Exposure Promotes Adult Atherogenesis and Mitochondrial Damage in Apolipoprotein E-/- Mice Fed a Chow Diet Circulation, December 14, 2004; 110(24): 3715 - 3720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C Hindmarsh Commentary: Catch-up growth in humans--a comment on poverty, birthweight, and infant weight gain in Hertfordshire Int. J. Epidemiol., December 1, 2004; 33(6): 1234 - 1235. [Full Text] [PDF]
|
|
|
|
 |
|
 P. D. Gluckman and M. A. Hanson Living with the Past: Evolution, Development, and Patterns of Disease Science, September 17, 2004; 305(5691): 1733 - 1736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Willms Early childhood obesity: a call for early surveillance and preventive measures Can. Med. Assoc. J., August 3, 2004; 171(3): 243 - 244. [Full Text] [PDF]
|
|
|
|
|
|
R. C. Whitaker Predicting Preschooler Obesity at Birth: The Role of Maternal Obesity in Early Pregnancy Pediatrics, July 1, 2004; 114(1): e29 - e36. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Power, L Li, O Manor, and G Davey Smith Combination of low birth weight and high adult body mass index: at what age is it established and what are its determinants? J Epidemiol Community Health, December 1, 2003; 57(12): 969 - 973. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Toschke, S. M. Montgomery, U. Pfeiffer, and R. von Kries Early Intrauterine Exposure to Tobacco-inhaled Products and Obesity Am. J. Epidemiol., December 1, 2003; 158(11): 1068 - 1074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Hypponen, G. D. Smith, and C. Power Effects of grandmothers' smoking in pregnancy on birth weight: intergenerational cohort study BMJ, October 18, 2003; 327(7420): 898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A Yanovski Rapid weight gain during infancy as a predictor of adult obesity Am. J. Clinical Nutrition, June 1, 2003; 77(6): 1350 - 1351. [Full Text] [PDF]
|
|
|
|
 |
|
 Lucina Arch. Dis. Child., January 1, 2003; 88(1): 94 - 94. [Full Text] [PDF]
|
|
|
|
|
|
G. A Bray Predicting obesity in adults from childhood and adolescent weight Am. J. Clinical Nutrition, September 1, 2002; 76(3): 497 - 498. [Full Text] [PDF]
|
|
|
|
|
|
J. van der Meulen Commentary: Maternal smoking during pregnancy and obesity in the offspring Int. J. Epidemiol., April 1, 2002; 31(2): 420 - 421. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||